Valproic Acid-induced Hyperammonemic Encephalopathy Research Articles

Valproic acid-induced hyperammonemic encephalopathy (VIHE) in a patient with Bipolar disorder: A case report and literature review

IntroductionValproic acid (VPA) is a valuable treatment for bipolar disorder, schizoaffective disorder, and agitation1. However, potential side-effects include sedation, headaches, tremors, ataxia, gastrointestinal issues, neural tube defect, 3 and mild hyperammonemia even in normal liver function test 1 and VPA level.ObjectivesTo illustrate clinical presentation of VIHE and provide literature review on post-VIHE treatment options.MethodsA 59-year-old male with PMH of Diabetes Mellitus, Hypertension, Hyperlipidemia, LVH, COPD, s/p CVA, and PPH of schizoaffective disorder, bipolar type. Patient stable on VPA 1250mg daily and Olanzapine 5mg daily for >2years until recent manic decompensation resulting to up-titration of VPA to 1500mg H.S. Thereafter, he presented with altered mental status, with VPA level (111.4 ug/ml), hyponatremia (119 mmol/L) and hyperammonemia (84 umol/L). Subsequently, admitted as a case of VIHE and hyponatremia.ResultsVPA has shown to cause hyperammonemia alone or when combined with antipsychotics6. VIHE reported in up to 47.7% of patients on VPA1, but symptomatic in approximately 10% of patients on VPA with blood ammonia level about 2-fold the normal range8. VIHE presents with confusion, ataxia, blurred vision, delirium, and seizures3. Treatment options include VPA discontinuation, switch to other mood stabilizers (lithium carbonate, lamotrigine), utilization of medications to lower blood ammonia levels (Lactulose, Rifaximin/Neomycin) ,3 antipsychotic monotherapy, and supplements (Levocarnitine or Carglumic acid) in the prevention, maintenance, and treatment of VIHE. These supplements can be added to VPA if the benefits of re-initiating or continuing VPA outweighs the risk3.ConclusionsFurther research is needed.DisclosureNo significant relationships.

Valproic acid-induced hyperammonemic encephalopathy: a clinical case

IntroductionValproic acid is a psychotropic drug used for several years, due to its properties as a mood stabilizer, being considered as first-line treatment for bipolar disorder. In addition to its teratogenic potential, which prevents its recommendation for the treatment of bipolar disorder in women of childbearing age, valproic acid is associated with some side effects, such as gastrointestinal symptoms, alopecia, weight gain, tremor or hepatotoxicity. Hyperammonemia is a side effect that is little described, but relatively frequent, and may progress to variable encephalopathy.ObjectivesThe authors describe a clinical case of a 48-year-old female patient, hospitalized due to a manic episode, who was prescribed valproic acid, in association with lorazepam and olanzapine.MethodsAfter three days on a dose of 1000mg of valproic acid, the patient began an acute condition of confusion, psychomotor retardation, temporal-spatial disorientation and ataxia. Infection, electrolyte disturbance and acute cerebral event were excluded. Noteworthy only hyperammonemia. Valproic acid was withdrawn and replaced by lithium, with the patient recovering from the confusional state two days later.ResultsHyperamonemic encephalopathy secondary to valproic acid was concluded. The mechanisms of valproic acid-linked hyperammonemia are not clear, although it appears to be independent of hepatotoxicity. The most studied hypotheses are related to glutamine reabsorption and serum levels carnitine in patients medicated with valproic acid.ConclusionsIt is essential that there is a high level of suspicion in clinicians for this secondary effect of valproic acid, in order to adequately treat the patient who presents with acute confusional conditions, not explained by other complications.DisclosureNo significant relationships.

Intracranial Arachnoid Cysts Presenting with First-Episode Mania and Subsequent Hyperammonemic Encephalopathy: A Case Report

Abstract Intracranial arachnoid cysts are often an incidental discovery in the course of neuroimaging for other conditions. While often asymptomatic, cysts which enlarge can cause mass or pressure effects on adjacent structures. We report a 33-year-old male patient who presented with first episode of manic symptoms. Following treatment with sodium valproate patient developed altered sensorium and was subsequently diagnosed with middle cranial fossa arachnoid cysts and valproic acid-induced hyperammonemic encephalopathy that was successfully treated with enteric lactulose. There are several case reports of arachnoid cysts presenting in patients with psychiatric disorders and debating whether these cysts are a cause or co-occurrence. In 16 reported patients, who had arachnoid cysts with psychiatric symptoms, 9 had cysts exerting mass/pressure effects. Three patients had surgical intervention and showed significant improvement following surgery. So did 1 patient who was treated with mannitol infusion. Intracranial arachnoid cysts may also present with atypical psychiatric symptoms or complicate the treatment process by way of poor response or treatment emergent adverse effects. There is an important role for thorough neurological examination, neuroimaging, and vigilant use of psychotropics in such patients.

Valproic acid-induced Hyperammonemic Encephalopathy

Valproic acid-induced Hyperammonemic Encephalopathy

T39. Valproic Acid-Induced Hyperammonemic Encephalopathy

T39. Valproic Acid-Induced Hyperammonemic Encephalopathy

Hyperammonemic Encephalopathy due to Valproic Acid and Topiramate Interaction.

Valproic acid-induced hyperammonemic encephalopathy is a rare yet serious adverse drug reaction. Medication interactions such a valproic acid and topiramate can precipitate an event. We present the case of a 52-year-old female that presented with acute mental status change and hypersomnolence due to hyperammonemia caused by a valproic acid derivative. The patient improved after withdrawal of the offending medications and treatment with lactulose. Clinicians should remain hypervigilant in monitoring for valproic acid-induced hyperammonemic encephalopathy and risk factors such as polypharmacy.

Valproic acid-induced hyperammonemic encephalopathy – a potentially fatal adverse drug reaction

BackgroundA patient with an early diagnosed epilepsy Valproic acid is one of the most widely used antiepileptic drugs. Hyperammonemic encephalopathy is a rare, but potentially fatal, adverse drug reaction to valproic acid.Case descriptionA patient with an early diagnosed epilepsy, treated with valproic acid, experienced an altered mental state after 10 days of treatment. Valproic acid serum levels were within limits, hepatic function tests were normal but ammonia levels were above the normal range.Valproic acid was stopped and the hyperammonemic encephalopathy was treated with lactulose 15 ml twice daily, metronidazole 250 mg four times daily and L-carnitine 1 g twice daily.Discussion and evaluationMonitoring liver function and ammonia levels should be recommended in patients taking valproic acid. The constraints of the pharmaceutical market had to be taken into consideration and limited the pharmacological options for this patient's treatment.ConclusionsIdiosyncratic symptomatic hyperammonemic encephalopathy is completely reversible, but can induce coma and even death, if not timely detected.Clinical pharmacists can help detecting adverse drug reactions and provide evidence based information for the treatment.

Levocarnitine for valproic-acid-induced hyperammonemic encephalopathy

The use of levocarnitine for the treatment of valproic-acid-induced hyperammonemic encephalopathy (VHE) is reviewed. VHE is generally characterized by an acute onset of impaired consciousness, focal neurologic symptoms, and increased seizure frequency. The exact mechanism of VHE is unclear but relates to the accumulation of toxic valproic acid metabolites and elevated ammonia levels. Carnitine is an essential cofactor in the proper metabolism of valproic acid and ammonia elimination. A lack of carnitine is thought to contribute to hyperammonemia. Valproic acid is thought to increase renal metabolism of glutamate and may contribute to ammonia production. Levocarnitine, the active isomer of carnitine, has been used to treat VHE resulting from valproic acid overdose as well as usual dosages of valproic acid. A literature search of PubMed was conducted for all English-language articles published from 1948 to May 2011 regarding the use of levocarnitine for VHE. Search terms included levocarnitine, l-carnitine, valproic acid, and hyperammonemia encephalopathy. Although large, randomized controlled trials of levocarnitine treatment in VHE are lacking, levocarnitine has been shown to be generally safe and effective in retrospective trials and case reports. Overall, there is more literature supporting the use of levocarnitine in VHE associated with acute overdose than with short- or long-term treatment with usual dosages of valproic acid. No adverse events related to levocarnitine therapy were reported in any of the literature reviewed. Prospective trials are needed to further support the efficacy and safety of levocarnitine in the treatment of VHE. Levocarnitine may be effective and appears to be safe in the treatment of VHE.

Valproate-associated Hyperammonemic Encephalopathy

The use of valproic acid (VPA) (also known as Depakote, Depakene, and others) frequently results in elevated plasma ammonia. In some people, hyperammonemia may be clinically significant, resulting in hyperammonemic encephalopathy, which may be severe. Valproic acid-induced hyperammonemic encephalopathy may occur in people with normal liver function, despite normal doses and serum levels of VPA. We describe 2 cases of valproic acid-induced hyperammonemic encephalopathy in patients with supratherapeutic VPA levels, although the condition has been described in people with normal VPA levels. With the increasing indications and off-label uses of VPA, family physicians should be aware of this potential complication of VPA and check ammonia levels in patients taking VPA who present with alterations in mental status. Treatment with L-carnitine may be beneficial in reducing ammonia levels.

Non-convulsive status epilepticus secondary to valproic acid-induced hyperammonemic encephalopathy

Valproic acid (VPA) may induce hyperammonemic encephalopathy. On the other hand, seizure-inducing effects of antiepileptic drugs (AEDs) may be a paradoxical reaction or a result of AED-induced encephalopathy (commonly induced by VPA). We present the case of a 19-year-old male who developed acute mental status changes consistent with encephalopathy evolving into repetitive seizures with oral automatisms induced by relatively small doses of VPA. Although serum hepatic enzymes, such as AST and ALT, were normal, serum ammonia concentration was high, i.e. 70 micromol/l (normal range 9-33 micromol/l). Administration of VPA was discontinued immediately after admission. The patient's condition improved during the second week of hospitalization and ammonium levels returned to normal. In conclusion, although uncommon, a possible induction of non-convulsive status epilepticus by valproate-induced hyperammonemic encephalopathy should be taken into account and properly managed by discontinuation of the drug.

Valproic Acid-Induced Hyperammonemic Encephalopathy

Objective To review the relevant literature concerning the biochemical mechanism(s) of valproic acid (VPA)-induced hyperammonemia in an attempt to present a unifying pathogenetic hypothesis. Data Sources The MEDLINE database (1966–July 2001) was searched for English-language articles and abstracts on VPA-induced hyperammonemia. References cited in relevant primary articles were also reviewed. Study Selection More than 150 original and review articles were evaluated, and the most relevant were selected. Data Extraction Clinically significant hyperammonemia is a rare adverse effect of VPA therapy. The exact pathogenesis of VPA-induced hyperammonemia remains unclear, but is likely to involve a variety of contributing and possibly overlapping biochemical steps. These include VPA drug concentration, indirect inhibition of ureagenesis by valproyl coenzyme A (CoA), direct suppression of the urea cycle enzymes, depletion of mitochondrial acetyl CoA and decreased production of N-acetylglutamate, depletion of carnitine stores, and increased glutamate dehydrogenase activity. Conclusions Hyperammonemic encephalopathy is a rare, but clinically important, adverse effect of VPA therapy. The biochemical basis for this association remains unclear. Awareness of this adverse reaction by healthcare personnel is important in early recognition, treatment, and prevention.